Loss of Pigment Epithelium Derived Factor Sensitizes C57BL/6J Mice to Light-Induced Retinal Damage.

Purpose: Pigment epithelium-derived factor (PEDF) is a neurotrophic glycoprotein secreted by the retinal pigment epithelium (RPE) that supports retinal photoreceptor health. Deficits in PEDF are associated with increased inflammation and retinal degeneration in aging and diabetic retinopathy. We hypothesized that light-induced stress in C57BL/6J mice deficient in PEDF would lead to increased retinal neuronal and RPE defects, impaired expression of neurotrophic factor Insulin-like growth factor 1 (IGF-1), and overactivation of Galectin-3-mediated inflammatory signaling.

Oral supplementation with Nicotinamide Riboside treatment protects RGCs in DBA/2J mouse model.

Purpose: The aim of this study was to test whether oral administration of nicotinamide riboside (NR), the nicotinamide adenine dinucleotide (NAD+) precursors, protect retina ganglion cells (RGCs) from neurodegeneration in DBA/2J (D2) mice, which is a widely used mouse model of age-related inherited glaucoma.

Method: Oral NR or NAM administration (NR low dose: 1150mg/kg; NR high dose: 4200mg/kg; NAM low dose group: 500mg/kg; NAM high dose: 2000mg/kg of body weight per day) essentially started when D2 mice were 4 or 9 months old and continued up to 12 months old. Control cohort identically received food/water without NAM or NR.

The forced-response method: A new chronometric approach to measure conflict processing.

Despite long-standing concerns about the use of free reaction times (RTs) in cognitive psychology, they remain a prevalent measure of conflict resolution. This report presents the forced-response method as a fresh approach to examine speed-accuracy trade-off functions (SATs) in conflict tasks. The method involves fixing the overall response time, varying the onset of stimuli, and observing response expression.

The temporal dynamics of visual attention.

Researchers have long debated how humans select relevant objects amid physically salient distractions. An increasingly popular view holds that the key to avoiding distractions lies in suppressing the attentional priority of a salient distractor. However, the precise mechanisms of distractor suppression remain elusive.

Myosin forces elicit an F-actin structural landscape that mediates mechanosensitive protein recognition.

Cells mechanically interface with their surroundings through cytoskeleton-linked adhesions, allowing them to sense physical cues that instruct development and drive diseases such as cancer. Contractile forces generated by myosin motor proteins mediate these mechanical signal transduction processes through unclear protein structural mechanisms. Here, we show that myosin forces elicit structural changes in actin filaments (F-actin) that modulate binding by the mechanosensitive adhesion protein α-catenin.

Myosin-5 varies its step length to carry cargo straight along the irregular F-actin track.

Molecular motors employ chemical energy to generate unidirectional mechanical output against a track while navigating a chaotic cellular environment, potential disorder on the track, and against Brownian motion. Nevertheless, decades of nanometer-precise optical studies suggest that myosin-5a, one of the prototypical molecular motors, takes uniform steps spanning 13 subunits (36 nm) along its F-actin track. Here, we use high-resolution interferometric scattering microscopy to reveal that myosin takes strides spanning 22 to 34 actin subunits, despite walking straight along the helical actin filament.

Compatibility of Standard Vagus Nerve Stimulation and Investigational Microburst Vagus Nerve Stimulation Therapy with fMRI.

Vagus nerve stimulation devices are conditionally approved for MR imaging with stimulation turned off, and the requirement to modify the stimulation settings may be a barrier to scanning in some radiology practices. There is increasing interest in studying the effects of stimulation during MR imaging/fMRI. This study evaluated the safety of standard and investigational microburst vagus nerve stimulation therapies during MR imaging/fMRI.

Pentosan Polysulfate Sodium Causes Diminished Function and Subtle Morphological Changes in Retina and RPE of Mice.

Purpose: There are numerous reports of a distinctive maculopathy in adults exposed to pentosan polysulfate sodium (PPS), a drug prescribed to treat bladder discomfort associated with interstitial cystitis. We tested whether PPS treatment of mice injures RPE or retina to provide insight into the etiology of the human condition.

Methods: Mice were fed PPS-supplemented chow over 14 months.

Molecular regulatory mechanism of human myosin-7a.

Myosin-7a is an actin-based motor protein essential for vision and hearing. Mutations of myosin-7a cause type 1 Usher syndrome, the most common and severe form of deafblindness in humans. The molecular mechanisms that govern its mechanochemistry remain poorly understood, primarily because of the difficulty of purifying stable intact protein.

Evaluating reduced-form modeling tools for simulating ozone and PM monetized health impacts.

Reduced-form modeling approaches are an increasingly popular way to rapidly estimate air quality and human health impacts related to changes in air pollutant emissions. These approaches reduce computation time by making simplifying assumptions about pollutant source characteristics, transport and chemistry. Two reduced form tools used by the Environmental Protection Agency in recent assessments are source apportionment-based benefit per ton (SA BPT) and source apportionment-based air quality surfaces (SABAQS).

A brain specific alternatively spliced isoform of nonmuscle myosin IIA lacks its mechanoenzymatic activities.

Recent genomic studies reported that 90 to 95% of human genes can undergo alternative splicing, by which multiple isoforms of proteins are synthesized. However, the functional consequences of most of the isoforms are largely unknown. Here, we report a novel alternatively spliced isoform of nonmuscle myosin IIA (NM IIA), called NM IIA2, which is generated by the inclusion of 21 amino acids near the actin-binding region (loop 2) of the head domain of heavy chains.

Myosin-5 varies its steps along the irregular F-actin track.

Molecular motors employ chemical energy to generate unidirectional mechanical output against a track. By contrast to the majority of macroscopic machines, they need to navigate a chaotic cellular environment, potential disorder in the track and Brownian motion. Nevertheless, decades of nanometer-precise optical studies suggest that myosin-5a, one of the prototypical molecular motors, takes uniform steps spanning 13 subunits (36 nm) along its F-actin track.

"It's a Different Conversation": Qualitative Analysis of Pediatric Home-based Hospice/Palliative Care Visits' Perceived Value.

Unlabelled: Home-based hospice and/or palliative care (HBHPC) is an important and increasingly utilized aspect of care for children with serious conditions-those with high mortality risk, which either impacts their quality of life or carries a significant caregiver burden. Provider home visits are a core feature; however, the travel time and human resource allocation are significant challenges. Balancing the appropriateness of this allocation requires further characterization of the value of home visits to families and identification of the value domains of HBHPC for caregivers.

Flagella-like beating of actin bundles driven by self-organized myosin waves.

Wave-like beating of eukaryotic cilia and flagella-threadlike protrusions found in many cells and microorganisms-is a classic example of spontaneous mechanical oscillations in biology. This type of self-organized active matter raises the question of the coordination mechanism between molecular motor activity and cytoskeletal filament bending. Here we show that in the presence of myosin motors, polymerizing actin filaments self-assemble into polar bundles that exhibit wave-like beating.

Deletion of histone demethylase (Kdm1a) during retinal development leads to defects in retinal function and structure.

Purpose: The purpose of this study was to investigate the role of Lysine specific demethylase 1 () in murine retinal development. LSD1 is a histone demethylase that can demethylate mono- and di-methyl groups on H3K4 and H3K9. Using Chx10-Cre and Rho-iCre75 driver lines, we generated novel transgenic mouse lines to delete in most retinal progenitor cells or specifically in rod photoreceptors.

A gene duplication of a septin reveals a developmentally regulated filament length control mechanism.

Septins are a family of conserved filament-forming proteins that function in multiple cellular processes. The number of septin genes within an organism varies, and higher eukaryotes express many septin isoforms due to alternative splicing. It is unclear if different combinations of septin proteins in complex alter the polymers' biophysical properties.

Association between prostate size and glandular tissue volume of the peripheral zone via novel combined MRI and histopathology: possible pathophysiological implications on prostate cancer development.

Purpose: Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are the two most prevalent urologic diseases affecting elderly men. An inverse relationship between BPH/prostate size and PCa incidence is well documented in the current literature, but the precise mechanism is poorly understood. This study aims to investigate the effect of total prostate volume on total glandular tissue volume of the peripheral zone via a novel combination of magnetic resonance imaging (MRI) and histo-anatomical imaging.

Patients with moderate to severe COVID-19 outcomes on remdesivir according to baseline 4C mortality score.

Background: Remdesivir was the first antiviral to show clinical benefit in patients with moderate-to-severe COVID-19. Previous trials demonstrated a faster time to recovery in hospitalized patients treated with remdesivir vs placebo. Current guidelines recommend treatment with remdesivir based on hospitalization status, oxygen requirements, and time from symptom onset.

Robotic-assisted laparoscopic pyelolithotomy with intracorporeal pyeloscopy in a horseshoe kidney.

Horseshoe kidneys are one of the most common congenital genitourinary malformations and can increase the complexity of common urologic procedures, especially nephrolithiasis. We present a patient who underwent robotic-assisted laparoscopic pyelolithotomy with intracorporeal pyeloscopy and stone basketing to treat a left lower pole stone burden located in a horseshoe kidney. This procedure provided benefits of expanded maneuverability, dexterity, and stability, which resulted in successful elimination of stone burden on post-operative imaging.

Decreasing Burnout and Improving Work Environment: The Impact of on a Pediatric Hematopoietic Cell Transplant Team.

Purpose: Oncology teams are challenged by BO, which may be alleviated by meaningful recognition. In this study, -altruistic acknowledgment-was implemented on a pediatric hematopoietic cell transplant unit to evaluate its impact on staff and work environment.

Methods: In this longitudinal, mixed-methods pilot study, interdisciplinary inpatient hematopoietic cell transplant providers received web-based education.

UK Biobank: a globally important resource for cancer research.

UK Biobank is a large-scale prospective study with deep phenotyping and genomic data. Its open-access policy allows researchers worldwide, from academia or industry, to perform health research in the public interest. Between 2006 and 2010, the study recruited 502,000 adults aged 40-69 years from the general population of the United Kingdom.

Comparison of Good Clinical Practice Inspection Processes for Marketing Applications Between the United States Food and Drug Administration and the European Medicines Agency.

Background: The U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) began collaboration on Good Clinical Practice (GCP) inspections for marketing applications since 2009.

Pericentrin interacts with Kinesin-1 to drive centriole motility.

Centrosome positioning is essential for their function. Typically, centrosomes are transported to various cellular locations through the interaction of centrosomal microtubules (MTs) with motor proteins anchored at the cortex or the nuclear surface. However, it remains unknown how centrioles migrate in cellular contexts in which they do not nucleate MTs.

Association Between Prostate Size and MRI Determined Quantitative Prostate Zonal Measurements.

Purpose: Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are the two most prevalent and common urologic diseases impacting elderly men. The current literature has well documented an inverse relationship between prostate/BPH-size and incidence of PCa, but the exact interaction between these two disease entities is not well understood. The purpose of this study is to analyze prostatic zonal measurements with magnetic resonance imaging (MRI) in order to investigate the dynamic changes of the transition zone (TZ) and peripheral zone (PZ) in response to prostate/BPH growth.